Background We examined the usefulness of erythrocyte-bound C4d (EC4d) to monitor disease activity in SLE. Methods: Data and blood samples were collected from three different studies, each of which included longitudinal evaluations using the Physicians Global Assessment (PGA) of disease activity and the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLE Disease Activity Index (SLEDAI), which was assessed without anti-double-stranded DNA (dsDNA) and low complement C3/ C4 (clinical SELENA-SLEDAI). EC4d levels were determined using flow cytometry; other laboratory measures included antibodies to dsDNA, C3 and C4 proteins. Relationships between clinical SELENA-SLEDAI, PGA and the laboratory measures were analysed using linear mixed effect models. Results: The three studies combined enrolled 124 patients with SLE (mean age 42 years, 97% women, 31% Caucasians and 34% African-Americans) followed for an average of 5 consecutive visits (range 2–13 visits). EC4d levels and low C3/C4 status were significantly associated the clinical SELENA-SLEDAI or PGA in each of the three study groups (p<0.05). Multivariate analysis revealed that EC4d levels (estimate=0.94±0.28) and low complement C3/C4 (estimate=1.24±0.43) were both independently and significantly associated with the clinical SELENA-SLEDAI (p<0.01) and PGA. EC4d levels were also associated with the clinical SELENA-SLEDAI (estimate: 1.20±0.29) and PGA (estimate=0.19±0.04) among patients with chronically low or normal C3/C4 (p<0.01). Anti-dsDNA titres were generally associated with disease activity. Conclusion: These data support the association of EC4d with disease activity regardless of complement C3/ C4 status and its usefulness in monitoring SLE disease. Additional studies will be required to support these validation data.

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AVISE CTD is a comprehensive autoimmune connective tissue disease (CTD) diagnostic tool that leverages the highest quality standards and scientific analysis to provide rheumatologists with actionable results.

AVISE CTD is a blood test that provides insight into the differential diagnosis among a host of challenging diseases to diagnose including:

– Lupus (SLE)
– Rheumatoid arthritis
– Sjögren’s syndrome
– Polymyositis and dermatomyositis
– Scleroderma/systemic sclerosis
– Anti-phospholipid syndrome
– Autoimmune thyroid disease – Hashimoto’s and Grave’s

AVISE testing incorporates several biomarkers that are exclusively available from Exagen, including CB-CAPs and anti-CarP, as well as novel markers not widely available including anti-C1q and anti-PS/PT.

Cell-Bound Complement Activation Products (or CB-CAPs) are stable biomarkers of complement activation, the key part of the disease process for the development of tissue damage in lupus. These biomarkers demonstrate excellent diagnostic performance over current diagnostic biomarkers alone.

Anti-Phosphatidylserine/prothrombin (PS/PT) – a complex antigen distinct from PS or PT alone that helps physicians assess a patient’s risk of thrombosis and pregnancy loss associated with antiphospholipid syndrome (APS). In addition, PS/PT has been found to correlate very strongly to APS manifestations

Anti-C1q helps physicians assess a patient’s risk of thrombosis and lupus nephritis.

Both anti-PS/PT and anti-C1q are included in the AVISE SLE Prognostic and can be ordered at the same time as AVISE CTD.

Physicians interested in ordering AVISE CTD can request a sample preparation guide that provides easy-to-follow instructions and the required materials, including a prepaid shipping label, ice pack and insulated interior to protect the specimens in transit.

Specimen collection tubes can also be provided upon request.

To request a kit, call 888.452-1522 or email us at [email protected]

Patients interested in having the test performed should present our physician request letter to their doctor.

AVISE CTD results are provided to the ordering physician within 5 business days from receipt of the sample.

AVISE CTD was developed after 15 years of research by Exagen and collaborators.

AVISE CTD is intended to be used for patients who have clinical suspicion of CTD and SLE due to clinical manifestations or related serologies. AVISE CTD has also been found to have clinical utility in differentiating +ANA primary fibromyalgia from SLE.

SLE associated markers:
– EC4d & BC4d
– Anti-Smith
– Anti-dsDNA (by ELISA and confirmation by Crithidia)
– ANA (by ELISA and IIF)

Extractable Nuclear Antigens Antibodies associated with autoimmune conditions that cause lupus-like symptoms:
– Anti-SS-A/Ro
– Anti-SS-B/La
– Anti-Scl-70
– Anti-U1RNP
– Anti-RNP70
– Anti-CENP
– Anti-Jo-1

Markers associated with rheumatoid arthritis:
– RF IgM
– RF IgA
– Anti-CCP
– Anti-CarP

Markers associated with Antiphospholipid syndrome, a common condition associated with SLE:
– Anti-Cardiolipin IgM
– Anti-Cardiolipin IgG
– Anti-B2-GP 1 IgM
– Anti-B2-GP 1 IgG

Markers associated with autoimmune thyroid disease:
– Anti-Thyroglobulin
– Anti-Thyroid Peroxidase

In a multicenter study including 794 subjects, AVISE CTD demonstrated superior performance over ANA and anti-dsDNA with:

33% increased specificity over ANA
48% increased sensitivity over anti-dsDNA
In addition, AVISE CTD’s scientifically proven CB-CAPs technology has also demonstrated a 22% increased sensitivity over C3/C4.
Putterman C, et al. Lupus Science & Medicine. 2014.

Yes, Exagen offers a financial assistance program for low income and self-pay patients. For more information, please visit: AVISE Insurance and Billing